Dataset Information

LncRNA PPP1R14B-AS1 Promotes Tumor Cell Proliferation and Migration via the Enhancement of Mitochondrial Respiration.

ABSTRACT: PPP1R14B-AS1 is an antisense long non-coding RNA with unknown functions. Herein, gene differential analyses were performed using the data of patients with liver cancer and lung adenocarcinoma (LUAD) from The Cancer Genome Atlas database. PPP1R14B-AS1 was found to be upregulated and also overexpressed in 10 other types of cancers. In addition, PPP1R14B-AS1 overexpression was associated with poor overall prognosis in eight cancers. Furthermore, PPPAR14B-AS1 upregulation was positively associated with worsening development of liver and LUAD cancers and related to poor disease-free survival. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses suggested that PPP1R14B-AS1 strongly participated in regulating cell aerobic respiration processes, such as mitochondrial electron respiration chain and NADH dehydrogenation processes. Cell cytoplasmic and nuclear RNA purification assessment results revealed that PPP1R14B-AS existed in the cell nucleus and cytoplasm. The knockdown of PPP1R14B-AS1 in HepG2 and A549 cells using PPP1R14B-AS1-specific siRNAs decreased mitochondrial respiration as demonstrated by the reduction in basal respiration and ATP production. Moreover, PPP1R14B-AS1 downregulation did not obviously affect cell glycolysis ability. Finally, PPP1R14B-AS1 inhibition inhibited HepG2 and A549 cell migration and proliferation. In summary, our study found for the first time that PPP1R14B-AS1 could be a potential biomarker for cancer diagnosis and that PPP1R14B-AS1 inhibition could be a potentially effective therapy.

SUBMITTER: Yang Y

PROVIDER: S-EPMC7686783 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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LncRNA PPP1R14B-AS1 Promotes Tumor Cell Proliferation and Migration via the Enhancement of Mitochondrial Respiration.

Yang Yibin Y Zhang Yuan Y Miao Lihong L Liao Weijie W Liao Weifang W

Frontiers in genetics 20201111

PPP1R14B-AS1 is an antisense long non-coding RNA with unknown functions. Herein, gene differential analyses were performed using the data of patients with liver cancer and lung adenocarcinoma (LUAD) from The Cancer Genome Atlas database. PPP1R14B-AS1 was found to be upregulated and also overexpressed in 10 other types of cancers. In addition, PPP1R14B-AS1 overexpression was associated with poor overall prognosis in eight cancers. Furthermore, PPPAR14B-AS1 upregulation was positively associated w ...[more]

PMID: 33262783

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Project description:GBM (Glioblastoma multiform) is the most malignant tumor type of the central nervous system and has poor diagnostic and clinical outcomes. LncRNAs (Long non-coding RNAs) have been reported to participate in multiple biological and pathological processes, but their underlying mechanism remains poorly understood. Here, we aimed to explore the role of the lncRNA HAS2-AS1 (HAS2 antisense RNA 1) in GBM. GSE103227 was analyzed, and qRT-PCR was performed to measure the expression of HAS2-AS1 in GBM. FISH (Fluorescence in situ hybridization) was performed to verify the localization of HAS2-AS1. The interaction between HAS2-AS1 and miR-137 (microRNA-137) was predicted by LncBook and miRcode followed by dual-luciferase reporter assays, and the relationships among HAS2-AS1, miR-137 and LSD1 (lysine-specific demethylase 1) were assessed by WB (western blot) and qRT-PCR. Colony formation and CCK-8 (cell counting kit-8) assays were performed as functional tests. In vivo, nude mice were used to confirm the function of HAS2-AS1. HAS2-AS1 expression was upregulated in GBM cell lines, and HAS2-AS1 was localized mainly in the cytoplasm. In vitro, high HAS2-AS1 expression promoted proliferation, and knockdown of HAS2-AS1 significantly inhibited proliferation. Furthermore, HAS2-AS1 functioned as a ceRNA (competing endogenous RNA) of miR-137, leading to the disinhibition of its downstream target LSD1. The miR-137 level was downregulated by HAS2-AS1 overexpression and upregulated by HAS2-AS1 knockdown. In a subsequent study, LSD1 expression was negatively regulated by miR-137, while miR-137 reversed the LSD1 expression levels caused by HAS2-AS1. These results were further supported by the nude mouse tumorigenesis experiment; compared with xenografts with high HAS2-AS1 expression, the group with low levels of HAS2-AS1 exhibited suppressed proliferation and better survival. We conclude that lncRNA HAS2-AS1 promotes proliferation by functioning as a miR-137 decoy to increase LSD1 levels and thus might be a possible biomarker for GBM.

Dataset Information

LncRNA PPP1R14B-AS1 Promotes Tumor Cell Proliferation and Migration via the Enhancement of Mitochondrial Respiration.

Publications

LncRNA PPP1R14B-AS1 Promotes Tumor Cell Proliferation and Migration via the Enhancement of Mitochondrial Respiration.

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